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Journal of Virology, April 1999, p. 2745-2751, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Drastic Fitness Loss in Human Immunodeficiency Virus Type 1 upon Serial Bottleneck Events

Eloisa Yuste,1 Sonsoles Sánchez-Palomino,1,dagger Concha Casado,1 Esteban Domingo,2 and Cecilio López-Galíndez1,*

Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid,1 and Centro de Biología Molecular "Severo Ochoa," CSIC-UAM, Universidad Autónoma, Cantoblanco, 28049 Madrid,2 Spain

Received 19 June 1998/Accepted 7 December 1998

Muller's ratchet predicts fitness losses in small populations of asexual organisms because of the irreversible accumulation of deleterious mutations and genetic drift. This effect should be enhanced if population bottlenecks intervene and fixation of mutations is not compensated by recombination. To study whether Muller's ratchet could operate in a retrovirus, 10 biological clones were derived from a human immunodeficiency virus type 1 (HIV-1) field isolate by MT-4 plaque assay. Each clone was subjected to 15 plaque-to-plaque passages. Surprisingly, genetic deterioration of viral clones was very drastic, and only 4 of the 10 initial clones were able to produce viable progeny after the serial plaque transfers. Two of the initial clones stopped forming plaques at passage 7, two others stopped at passage 13, and only four of the remaining six clones yielded infectious virus. Of these four, three displayed important fitness losses. Thus, despite virions carrying two copies of genomic RNA and the system displaying frequent recombination, HIV-1 manifested a drastic fitness loss as a result of an accentuation of Muller's ratchet effect.

* Corresponding author. Mailing address: Servicio de Virología Molecular, Centro Nacional de Biología Fundamental, Instituto de Salud Carlos III, Majadahonda, 28220 Madrid, Spain. Phone: 34 91 509 79 03. Fax: 34 91 509 79 18. E-mail: clopez{at}isciii.es.

dagger Present address: Centro de Investigación Hospital 12 de Octubre, 28041 Madrid, Spain.

Journal of Virology, April 1999, p. 2745-2751, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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